Impact Analysis of False Data Injection Attack on Smart Grid State Estimation Under Random Packet Losses

Supervisory control and data acquisition (SCADA) system has been widely used in traditional power systems for operation and control. As increasingly more ICT technologies are deployed to improve the smartness of the power grid, cyber security is becoming an important issue in the development of smart grids, for example, false data injection attack (FDIA) poses a serious threat. The paper analyzes the impact of false data injection attack on smart grid state estimation under random packet losses. First, a measurement model of power grids under random packet loss is established, and an attack vector range that can fool the attack detector is acquired. Then, a mean square error matrix of weighted least squares estimation is proposed, taking into account potential false data injection attacks. A IEEE-14 nodes system is used to evaluate the performance of the weighted least squares state estimation under three different scenarios, namely false data injection attack only, random packet loss only, and under both random packet loss and false data injection attack

MARK/Par1 Kinase Is Activated Downstream of NMDA Receptors through a PKA-Dependent Mechanism

<div><p>The Par1 kinases, also known as microtubule affinity-regulating kinases (MARKs), are important for the establishment of cell polarity from worms to mammals. Dysregulation of these kinases has been implicated in autism, Alzheimer’s disease and cancer. Despite their important function in health and disease, it has been unclear how the activity of MARK/Par1 is regulated by signals from cell surface receptors. Here we show that MARK/Par1 is activated downstream of NMDA receptors in primary hippocampal neurons. Further, we show that this activation is dependent on protein kinase A (PKA), through the phosphorylation of Ser431 of Par4/LKB1, the major upstream kinase of MARK/Par1. Together, our data reveal a novel mechanism by which MARK/Par1 is activated at the neuronal synapse.</p></div

MARK/Par1 is activated by NMDA receptors through PKA.

<p>a. Hippocampal neurons were treated with 4-AP and picrotoxin for 10 minutes. For inhibition of PKA, H-89 was included in the pretreatment and during 4-AP/PTX stimulation. Neurons were lysed and immunoblotted with the indicated antibodies. b. Quantifications of blots in (a). Data are Mean ± SD, *p<0.01, n = 5. c. Hippocampal neurons were treated with DMSO (Control) or 10 μM forskolin (Fsk) for 10 minutes. Neurons were lysed and immunoblotted with the indicated antibodies. d. Quantifications of blots in (c). Data are Mean ± SD, *p<0.01, n = 4.</p

Par4/LKB1 is activated by NMDA receptors through PKA.

<p>a. Hippocampal neurons were treated with 4-AP and picrotoxin for 10 minutes. For inhibition of PKA, H-89 was included in the pretreatment and during 4-AP/PTX stimulation. Neurons were lysed and immunoblotted with the indicated antibodies. b. Quantifications of blots in (a). Data are Mean ± SD, *p<0.01, n = 4. c. Hippocampal neurons were treated with DMSO (Control) or 10 μM forskolin (Fsk) for 10 minutes. Neurons were lysed and immunoblotted with the indicated antibodies. d. Quantifications of blots in (c). Data are Mean ± SD, *p<0.001, n = 5.</p

MARK/Par1 is activated by NMDA receptors.

<p>a. Hippocampal neurons were pretreated with CNQX and TTX for 30 minutes, then stimulated with 50 μM of NMDA for 5 min. For inhibition of NMDA receptors, APV was included in the pretreatment and during NMDA stimulation. Neurons were lysed and immunoblotted with the indicated antibodies. b. Quantifications of blots in (a). Data are Mean ± SD, *p<0.05, **p<0.01, n = 4. c. Hippocampal neurons were pretreated with CNQX and TTX for 30 minutes, then stimulated with 50 μM of NMDA for 5 min. For EGTA treatment, EGTA was included in the pretreatment and during NMDA stimulation. Neurons were lysed and immunoblotted with the indicated antibodies. d. Quantifications of blots in (c). Data are Mean ± SD, *p<0.01, n = 4. e. Hippocampal neurons were treated with 4-AP and picrotoxin for 10 minutes. For inhibition of NMDA receptors, APV was included in the pretreatment and during 4-AP/PTX stimulation. Neurons were lysed and immunoblotted with the indicated antibodies. f. Quantifications of blots in (e). Data are Mean ± SD, *p<0.005, n = 5.</p

MARK/Par1 is regulated by synaptic activity.

<p>Hippocampal neurons were treated with either DMSO (Control) or 10 μM of picrotoxin (PTX) for one hour. After treatment, neurons were lysed and immunoblotted with the indicated antibodies. Representative blots are shown in (a) and quantifications are shown in (b), expressed as Mean ± SD. *p<0.01, n = 5.</p

Loss of Par1b/MARK2 primes microglia during brain development and enhances their sensitivity to injury

Abstract Background Microglia, the resident immune cells of the brain, exhibit various morphologies that correlate with their functions under physiological and pathological conditions. In conditions such as aging and stress, microglia priming occurs, which leads to altered morphology and lower threshold for activation upon further insult. However, the molecular mechanisms that lead to microglia priming are unclear. Methods To understand the role of Par1b/MARK2 in microglia, we first expressed shRNA targeting luciferase or Par1b/MARK2 in primary microglial cells and imaged the cells using fluorescent microscopy to analyze for morphological changes. A phagocytosis assay was then used to assess functional changes. We then moved in vivo and used a Par1b/MARK2 knockout mouse model to assess for changes in microglia density, morphology, and phagocytosis using immunohistochemistry, confocal imaging, and 3D image reconstruction. Next, we used two-photon in vivo imaging in live Par1b/MARK2 deficient mice to examine microglia dynamics. In addition, a controlled-cortical impact injury was performed on wild-type and Par1b/MARK2-deficient mice and microglial response was determined by confocal imaging. Finally, to help rule out non-cell autonomous effects, we analyzed apoptosis by confocal imaging, cytokine levels by multiplex ELISA, and blood-brain barrier permeability using Evans Blue assay. Results Here, we show that loss of the cell polarity protein Par1b/MARK2 facilitates the activation of primary microglia in culture. We next found that microglia in Par1b/MARK2 deficient mice show increased density and a hypertrophic morphology. These morphological changes are accompanied with alterations in microglia functional responses including increased phagocytosis of neuronal particles early in development and decreased surveillance of the brain parenchyma, all reminiscent of a primed phenotype. Consistent with this, we found that microglia in Par1b/MARK2 deficient mice have a significantly lower threshold for activation upon injury. Conclusions Together, our studies show that loss of Par1b/MARK2 switches microglia from a surveillant to a primed state during development, resulting in an increased neuroinflammatory response to insults

Loss of the polarity protein Par3 promotes dendritic spine neoteny and enhances learning and memory

Summary: The Par3 polarity protein is critical for subcellular compartmentalization in different developmental processes. Variants of PARD3, encoding PAR3, are associated with intelligence and neurodevelopmental disorders. However, the role of Par3 in glutamatergic synapse formation and cognitive functions in vivo remains unknown. Here, we show that forebrain-specific Par3 conditional knockout leads to increased long, thin dendritic spines in vivo. In addition, we observed a decrease in the amplitude of miniature excitatory postsynaptic currents. Surprisingly, loss of Par3 enhances hippocampal-dependent spatial learning and memory and repetitive behavior. Phosphoproteomic analysis revealed proteins regulating cytoskeletal dynamics are significantly dysregulated downstream of Par3. Mechanistically, we found Par3 deletion causes increased Rac1 activation and dysregulated microtubule dynamics through CAMSAP2. Together, our data reveal an unexpected role for Par3 as a molecular gatekeeper in regulating the pool of immature dendritic spines, a rate-limiting step of learning and memory, through modulating Rac1 activation and microtubule dynamics in vivo